Tourette Syndrome (TS) is a debilitating and chronic neuropsychiatric disorder. Haloperidol is currently the drug of first choice in the treatment of TS but it frequently causes severe side effects which hamper its therapeutic usefulness. Pimozide has only recently been approved by the F. D. A. for use in TS and it is currently used only if treatment with haloperidol is unsuccessful. Pimozide has been demonstrated to be efficacious in TS but a direct comparison with haloperidol has not been done. The literature suggests that pimozide may have fewer side effects and may produce less cognitive impairment associated with therapeutic doses than haloperidol. The specific aim of this proposal is to determine the relative efficacy of pimozide and haloperidol utilizing a placebo controlled crossover design in a group of thirty six children suffering from TS. Three treatment conditions (haloperidol, pimozide, placebo) will be randomly assigned in a balanced fashion with two week washout periods between crossovers and six weeks on each treatment. The protocol will mimic clinical practice by aiming for a 70% reduction of tic symptoms using a flexible dose paradigm below 12 mg/day for each drug. The individualized dosing will allow relative toxicity to be compared at equivalent efficacies. A comparison of pimozide and haloperidol at their "most efficacious" dose will be made from data gathered at the end of six weeks on each medication. Characteristics unique to this proposal in comparison to the literature are the following: 1) a multidimensional approach to assessment of differential effects of haloperidol and pimozide via neurologic, cognitive, social, behavioral, and school performance outcome variables, 2) dose-response assessment to provide therapeutic and toxic ranges for these drugs in TS and where appropriate, therapeutic plasma concentration ranges to facilitate a targeting of the dose into a therapeutic range to avoid side effects. The proposal has important clinical implications in the treatment of children with TS if pimozide proves to have significant advantages over haloperidol in terms of efficacy and fewer side effects.